Among the various anorectal and colonic diseases, hemorrhoids occupy a prominent position and have been the subject of numerous clinical studies. Hemorrhoidal disease is characterised by bleeding, without any pain. Fresh blood spots occur immediately, on defecation. However, pain occurs when the hemorrhoids are secondarily infected, or complicated by thrombosis and anal fissures. Hemorrhoids can be caused by a variety of factors including hormones, genes, inflammation, infection, constipation, exercise, vascular stasis, diet, strain, physical stance in defecation, loss of connective tissue elasticity with age etc. The symptoms most widely recognized are bleeding, pain and prolapse (Hyams and Philpot, 1970; Smith, 1987). These may be accompanied by thrombosis, pruritis, edema etc. Hemorrhoids can be treated through reduction of inflammation and pain, haemostasis, wound healing and protection of vascular walls. Thus, an effective treatment of acute hemorrhoidal attacks should not only provide relief as early as 2-3 days after initiation of the treatment, but also reduce the recurrence of such attacks.
There exist several procedures for the treatment of hemorrhoids. WO8803398 patent application discloses surgical dressings for such treatment. Patents have been granted in respect of surgical devices such as European patent no. 0095142. U.S. Pat. No. 4,621,635 has been granted for the use of lasers in the treatment of hemorrhoids. The techniques of cryopharmacotherapy and electrochemical techniques for treatment of hemorrhoids have also been patented vide European patent no. 0091405 and European patent no. 0116688, respectively. However, the biggest drawbacks of the above are the involvement of medical experts beyond mere prescription of medicines and probable hospitalization. Also, some of them are physically and/or psychologically unpleasant in application for treating such diseases.
Several patents (U.S. Pat. Nos. 4,160,148, 4,508,728, 4,797,392, 4,518,583 and 5,234,914) have been granted in respect of compositions containing certain wound healing agents to provide symptomatic relief, by promoting tissue repair, reducing inflammation and encouraging wound healing. Some of them like U.S. Pat. Nos. 4,518,583 and 5,234,914 contain antimicrobial agents. These compositions, however, only relieve symptoms associated with inflammation, like heat, itching, redness, pain and swelling.
A number of compositions for the treatment of anorectal diseases (including hemorrhoids) are based on the anesthetic and vasoconstrictive properties of the constituents, but these provide only temporary symptomatic relief.
Patents in the United States of America (U.S. Pat. Nos. 4,613,498, 4,626,433, 5,166,132, 5,219,880, 5,234,914 and 4,797,392) and Europe (European patents nos. 0225832 and 0513442) have been granted in respect of compositions with varying constituents, for topical application in the form of suitable and acceptable pharmaceutical carriers, such as salts, ointments, etc., with organic, inorganic or biological active agents. However, these compositions provide only temporary relief and are limited to local application and cannot be used for systemic use or oral administration.
A topical treatment for hemorrhoidal pain and for spasms of the sphincters and muscles located in the GI tract is disclosed in a granted patent (U.S. Pat. No. 5,595,753), which includes amino acid L-arginine in a pharmaceutically acceptable carrier. Another U.S. Pat. No. 5,591,436 has been granted for a composition for dietary supplement for the treatment of hemorrhoids. The composition comprises 60% to 95% Indian Barberry by weight; 4.8% to 38% Nagkesar by weight; and 0.2% to 2% Margosa tree leaves by weight.
Another U.S. Pat. No. 5,562,906 discloses the use of bark or berries of the species Xanthoxylum clava herculis L and Xanthoxylum americanum Hill, both of the yellow wood tree family, are employed for the treatment of hemorrhoids and other membrane and capillary disorders of the veins and arteries. Improved strength and flexibility of the veins, arteries and their constituent structures is obtained.
The flavonoidal constituents present in the extract of Euphorbia Prostrata are reported to have anti-inflammatory properties. The phenolic compounds like ellagic and gallic acids and tannins are reported to have anti-inflammatory, haemostatic, gastro-protective and wound healing properties.
Other plants containing flavonoids including apigenin glycosides and luteolin glycosides are Ixora arborea (Rubiaceae), Bommeria hispida (Pteridaceae), Adenocalymma alliaceum (Bignoniaceae), Thalictrum thunbergii (Ranunculaceae), Perilla frutescens (Labiateae), Chrysenthemum indicum, C. coronarium and Matricaria chamomilla (Compositae), Thymus membranaceous (Labiateae), Digitalis lanata (Scrophulariaceae), Cuminum cyminum and Petroselinum (Umbelliferae). Several species of Euphorbia like Euphorbia minuta, Euphorbia microphylla, Euphorbia granulata (Euphorbiaceae) contain both apigenin and luteolin. Ellagic acid and other phenolic acids have been reported from different species of Euphorbia. 
The safety of various components of the Euphorbia extract has been reported in the literature. Some of the reports also claim anti-mutagenic/anti-carcinogenic/anti-genotoxic properties of the components of the Euphorbia extract.
An Indian Pat. No. 186803 and several other patents (Australia, No. 698407; China, No. CN 1102387C; Europe, No. 868914; Russia, No. 2174396; South Africa, No. 97/2900; South Korea, No. 281679 and U.S., Pat. No. 5,858,371) have been granted to this applicant for a composition comprising a flavonoid containing extract of Euphorbia prostrata for treatment of anorectal and colonic diseases. However, the presence of the phenolic compounds those are therapeutically useful for treatment of anorectal and colonic diseases due to their hemostatic and astringent properties, did not exist in the claimed extract. The process of extraction claimed in the said patent comprised of an intermediate step of treating the concentrated extract with hot water (80-90° C.); which resulted in the loss of especially the phenolic compounds from the extract, since they were washed out with the water. It has been surprisingly found by the inventors of the present invention that the presence of the phenolic compounds like ellagic acid, gallic acid and tannins comprising of these acids makes the claimed extract more effective for treatment of hemorrhoids and other colonic diseases, as the phenolic compounds are known mucoprotective agents. The antimicrobial properties of these phenolic compounds further prevent secondary infections often accompanied with hemorrhoids, fissures, fistulas etc. The present invention describes an improved process for the preparation of the Euphorbia prostrata extract thus resulting in an improved composition of the said extract. The previously essential step of treatment of the concentrated extract with hot water has been removed in the present invention since it was found that the water soluble portion contains substantial amount of phenolic compounds; instead washing the said concentrated extract was done directly with non-polar solvent where only waxy materials and pigments are removed and there is no significant loss of phenolic compounds, followed by preferably re-extracting the washed polar extract in a medium polarity organic solvent followed by distilling, dehydrating and finally drying the extract.
The inventors have further researched, and have found that the novel flavonoid and phenolic compounds containing extract of Euphorbia prostrata disclosed in the present invention exhibits improved pharmacological response in comparison to existing compositions employing flavonoids either from Euphorbia or other sources. Further, the extraction procedure of the disclosed Euphorbia Prostrata extract in the present invention is more cost effective and less time consuming in comparison to that of existing compositions employing flavonoids isolated from Euphorbia prostrata. The commercial implications of the improved and economic extraction procedure led the inventors to re-establish the pharmacological and toxicological validity of the new extract. The results were strikingly better than those of the equivalent flavonoid doses of the more purified extract of Euphorbia prostrata as disclosed earlier.
The present invention provides pharmaceutical compositions for the long-term management of anorectal diseases including hemorrhoids, and colonic diseases that are safe and painless to administer and have long-term effectiveness. The compositions of the present invention have improved efficacy and safety and are economical to manufacture.